Stem Cell Therapy for Kidney diseases: Important facts that you must know

You must have heard of the miraculous stem cell therapy that has been touted as a one stop solution for various disorders from preventing diabetes to even curing cancer. How much of this is really true and what is the state of art currently in stem cell therapy or regenerative medicine as it is generally called?

 

What are Stem Cells ?

Life begins from a single cell. These cells, during early development, rapidly divide and then differentiate to form all the components of the body. These are the two main characteristics of stem cells - to be able to keep dividing and surviving infinitely (self renewal) and to have the ability to form any part of the body (also called pluripotency). These make them an ideal candidate for therapy.

Self renewal enables researchers to produce enough quantity of these cells required for treatment. Pluripotency allows these cells to differentiate to healthy tissue from any part of the body. To treat a heart disorder, we could simply grow stem cells in a lab, induce them to produce healthy heart tissue and then inject it to the heart to replace the diseased or damaged tissue. Although powerful, this solution is not as simple as it sounds and there are issues associated with this.

 

Firstly, the stem cells that we have spoken of till now are the ones present during early development called embryonic stem cells since they are present in the embryonic stage. Obviously, these cells cannot be extracted easily and are under strict ethical regulations. Currently, these cells are mostly studied in animals or obtained from discarded human IVF embryos after an intense process of review and authorisation only allowed to be used in research.

A form of these stem cells are also present in adults called adult stem cells. However, these are present in small quantities and are generally restricted in terms of their potency. For example, cells called hematopoietic stem cells (HSCs)  are present in the bone marrow and aid in the formation of all types of blood cells. Essentially, these are the cells which help replenish red blood cells after they die every 120 days. Although the HSCs can form various types of blood cells they are not capable of forming other tissue types like the eye or kidney. Hence, the adult stem cells are called multipotent instead of pluripotent.

Therefore, adult stem cells may also be used for stem cell therapy but they are not as easy to extract and grow nor are they capable of working for all organ systems. Another source of HSCs is umbilical cord and placenta of newborns. Umbilical cords can be easily stored by freezing them and do not involve any ethical considerations since they would have otherwise been thrown away.

 

Secondly, appropriate signals and conditions need to be provided to the stem cells to obtain the desired cell type. Research is still being conducted on this and we do not yet have the formula to obtain every cell type in the body from stem cells. These cells also need to be present in a form which can maintain the biological activity of the cells. Commonly, these are in the form of infusions and injections to introduce them directly into the desired site.

Taking these cells orally will not work, since the cells will just be destroyed by the enzymes and pH of our  gastrointestinal system and never reach the desired site in an active form. It is also essential that these cells are obtained from other matched human donors and animal stem cell supplementation will be rejected by the body as foreign material and destroyed.

Thirdly, there is an immense risk associated with injecting stem cells in the body. As mentioned, they are capable of self renewal and may lead to development of tumors in the body. There may be adverse reactions to these cells at the site of injection or they may form inappropriate cell types at this site and have unknown consequences.

A lot of work is being done to workaround these obstacles. For example, we can now generate embryonic-like stem cells in the lab from almost any cell type including blood and skin. These are called induced pluripotent stem cells. This process is not currently suitable for clinics since it uses viral vectors for this transformation. However, once efforts to do this safely are successful we could potentially take blood or skin cells from the patient themselves, transform them to stem cells and then to desired cell type in the lab and re-inject them into the patient for therapy. Simultaneously efforts are being made to figure out all the different types of cells that can be obtained from an individual's harvestable adult stem cells. Both these methods would allow us to utilise the patient's own cells instead of depending on donors reducing the risk of rejection and adverse reactions.

Stem cell therapy in kidney diseases

Around 115.5 million people in India suffered from chronic kidney disease according to an estimate from 2017. Kidney diseases are highly debilitating and end stage kidney diseases can only be treated by maintenance dialysis or kidney transplant. Dialysis greatly reduces the quality of life and is expensive whereas kidney transplant entirely depends on availability of suitable donors. In this context, stem cells based therapy could be extremely valuable for treating renal diseases. Promising results have been obtained in animal studies for treating kidney diseases using both embryonic stem cells and induced pluripotent stem cells. They however, have certain drawbacks mentioned before and are still in the preclinical phase.

Another option for treating kidney diseases is the use of mesenchymal stem cells (MSCs) which form bone cells and fat cells in the body. These are a class of adult stem cells that can be obtained from  a variety of tissues including bone marrow, adipocytes or umbilical cord blood. An important characteristic of MSCs is the absence of certain molecules on their surface which generally trigger immunogenic reactions. This makes them safer to use and can be potentially transplanted from any individual without fear of rejection. MSC based therapies have been successful in acute kidney disease, chronic kidney disease, diabetic nephropathy, lupus nephritis, polycystic kidney disease and renovascular disease. MSCs not only home to the injured site but also secrete molecules that promote kidney repair and protection and prevent inflammation. These results are from preclinical studies and clinical trials to test their efficacy are underway. Around 40 clinical trials are ongoing worldwide to study the safety and efficacy of MSCs in treatment of kidney diseases. It would probably take another 10 years to get results of these clinical trials and obtain approvals to bring these treatments to the clinics.

Kidneys may also have a pool of adult stem cells which are only capable of differentiating to renal tissue. They are known as renal progenitor cells and efforts are ongoing to identify and isolate these cells. Renal progenitor cells replace the renal cells lost during normal physiological processes. It was also observed from some studies that the adult kidney is capable of limited repair and regeneration after injury which could be due to the presence of these renal progenitor cells. This research is still in very early stages but could open up a new avenue for the treatment of kidney disease.

 

The Health Sciences Authority and US Food and Drug Administration have issued warnings about illegal and potentially harmful stem cell therapy products and urge patients to verify and research thoroughly the approvals obtained by clinics providing stem cell therapy. The US FDA approved list of cell therapy products can be seen here.

 

Indian Council of Medical Research states that the only approved stem cell therapies are for treatment of genetic blood system disorders or blood cancers using cord blood or bone marrow derived stem cells. Treatments for other disorders using stem cells may be a part of clinical trials but are not approved therapy.

 

Patients must verify that the institute has obtained necessary approvals for conducting clinical trials. It is important to remember that clinical trials are a way to test the efficacies of different treatments and they are not guaranteed to be safe or effective. Stem cell therapy is an immensely attractive field of medicine and an active area of research. But a lot more work needs to be done for us to realise this potential and bring this therapy to clinics.

 

 

References:

Liu, Dongwei, et al. "Stem cells: a potential treatment option for kidney diseases." Stem cell research & therapy 11.1 (2020): 1-20.

Bikbov, Boris, et al. "Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017." The Lancet 395.10225 (2020): 709-733.

 

Profile

Dr. Dhruti Patwardhan is a research scientist with Nference Labs which works in drug development and discovery using data analysis. After completing her MSc in Biotechnology, she did her PhD in Neuroscience at the Indian Institute of Science (IISC) where she worked on generating disease models in the lab using embryonic and induced pluripotent stem cells.

Posted in Treatment for CKD on August 24 2021 at 07:03 PM
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